BIOORGANIC CHEMISTRY
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2020
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IF 4.831
Zhe Zhou,Jing Long,Yuan Wang,YaYun Li,Xu Zhang,Ling Tang,Qi Chang,Zhuo Chen,GaoYun Hu,Shuo Hu,QianBin Li,Cong Peng,Xiang Chen
CD147 is a transmembrane glycoprotein and a member of immunoglobulin superfamily, is strongly expressed in melanoma cells. CD147 has a pivotal role in tumor development. Therefore, it is a potential drug target for melanoma. In this article, we report the discovery of the first CD147 protein proteolysis targeting chimeras (PROTACs) derived from the natural product pseudolaric acid B (PAB). The representative compound 6a effectively induced degradation of CD147 and inhibited melanoma cells in vitro and in vivo. 6a could be used as the novel type of anticancer agent or as a part of the molecular biology research toolkit used in the gain-of-function study of the dynamic roles of CD147 in cancer networks.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2026
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IF 2.5
Wenhao Chen,Haoyun Bai,Quan Zhang,Jingjing Yang,Shengyu Zhou,Du Feng,Shengli Han
Established a universal screening platform for CD147-targeted therapeutics. • Integrated the CMC-HPLC system with mass spectrometry (MS) for the identification of unknown compounds. • Two bioactive constituents from Magnolia officinalis, directly interact with CD147. Hepatocellular carcinoma (HCC) is one of the most prevalent digestive malignancies, with CD147 emerging as a promising therapeutic target for HCC. To date, no natural bioactive components targeting CD147 for anti-HCC therapy have been explicitly reported. Given the low toxicity and favorable efficacy of natural small-molecule drugs, identifying and investigating CD147-targeted natural agents is imperative. In this study, based on cell membrane chromatography (CMC) and SNAP-tag protein labeling technology, we constructed a CD147-SNAP-tag-CMC/HPLC-MS two-dimensional coupled system to screen CD147-binding components from Magnolia officinalis , followed by ligand-receptor affinity verification, in vitro pharmacological evaluation, and downstream molecular mechanism validation. Two bioactive compounds, honokiol and magnolol, were successfully identified: both exhibit strong CD147 binding affinity, effectively suppress HCC cell migration, and exert their functions by regulating the CD147/integrin-FAK-paxillin pathway as confirmed by Western blotting. Collectively, the established two-dimensional system serves as a universal platform for CD147-targeted component screening. This study is the first to reveal the strong CD147 affinity of honokiol and magnolol and their anti-migratory effect on HCC cells via modulating the aforementioned pathway.
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PubMed
高影响因子
CANCER RESEARCH
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2024
·Vol. 84
·期 21
·3538-3555
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IF 12.5
Wang Xinzhi,Qu Yi,Xu Qianqian,Jiang Zeyu,Wang Hang,Lin Binyan,Cao Zehong,Pan Yuqi,Li Sheng,Hu Yili,Yang Hui,He Li,Chang Hang,Hang Bo,Wen Hongmei,Wu Hao,Mao Jian-Hua
Metastasis to the lungs is a leading cause of death for patients with breast cancer. Therefore, effective therapies are urgently needed to prevent and treat lung metastasis. In this study, we uncovered a mechanism by which NAD(P)H:quinone oxidoreductase 1 (NQO1) orchestrates lung metastasis. NQO1 stabilized and upregulated peptidyl-prolyl cis-trans isomerase A (PPIA), a chaperone that regulates protein conformation and activity, by preventing its oxidation at a critical cysteine residue C161. PPIA subsequently activated CD147, a membrane protein that facilitates cell invasion. Moreover, NQO1-induced secretion of PPIA modulated the immune landscape of both primary and lung metastatic sites. Secreted PPIA engaged CD147 on neutrophils and triggered the release of neutrophil extracellular traps (NET) and neutrophil elastase, which enhanced tumor progression, invasiveness, and lung colonization. Pharmacological targeting of PPIA effectively inhibited NQO1-mediated breast cancer lung metastasis. These findings reveal a previously unrecognized NQO1-PPIA-CD147-NET axis that drives breast cancer lung metastasis. Inhibiting this axis is a potential therapeutic strategy to limit lung metastasis in patients with breast cancer. Significance: NQO1 stabilizes and promotes the secretion of PPIA to activate CD147 in neutrophils and stimulate NET formation, promoting breast cancer lung metastasis and providing therapeutic targets for this fatal condition.
研究领域:
癌症生物学
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免疫学
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分子生物学
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DOI
高影响因子
LANGMUIR
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2022
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IF 4.331
Yao Wang,Yuanli Wang,Fangrong Hu,Lizhen Zeng,Zhencheng Chen,Mingzhu Jiang,Shangjun Lin,Wei Guo,Dongxia Li
Owing to their stability in bodily fluids, exosomes have attracted increased attention as colorectal cancer (CRC) biomarkers for early diagnosis. To validate the potential of the plasma exosomes as a novel biomarker for the monitoring of CRC, we demonstrated a terahertz (THz) metamaterials (MMs) biosensor for the detection of exosomes in this work. The biosensor with two resonant frequencies is designed using full wave electromagnetic simulation software based on the finite integration time domain (FITD) method and fabricated by a surface micromachining process. The biosensor surface is first modified using Au nanoparticles (AuNPs), and then, anti-KRAS and anti-CD147, which are specific to the exosomes, are modified on the AuNPs assembled with HS-poly(ethylene glycol)-COOH (HS-PEG-COOH). Exosomes used in the experiment are extracted via the instructions in the exosomes isolation and purification kit and identified by using transmission electron microscopy (TEM), Western blot (WB), and nanoparticle tracking analysis (NTA). The biosensor covered with plasma-derived exosomes of CRC patients has a different resonance frequency shift compared to that with healthy-control-derived exosomes. This study proposes an emerging and quick method for diagnosing the CRC.
研究领域:
生物医学工程
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癌症诊断
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纳米技术
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DOI
PubMed
高影响因子
Cell Death & Disease
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2026
·Vol. 17
·期 1
·750
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IF 12.2
Luomeng Qian,Ping Chen,Bo Wang,Qing Zhang,Yuan Guo,Jie Cui,Ran Ding,Hongkai Zhang,Sihe Zhang
Sorafenib is a widely used targeting drug for hepatocellular carcinoma (HCC) patients; however, sorafenib resistance poses a significant clinical challenge. Hypoxia and extracellular vesicles (EVs) induce vasculogenic mimicry (VM) which is linked to sorafenib resistance in HCC. Migrasomes (Migs), the newly discovered large EVs, foster HCC malignant phenotypes by facilitating the intercellular transfer of functional molecules. Despite these advancements, the precise mechanism by which Migs cause sorafenib resistance is still unknown. In this study, we found that hypoxia upregulates the Migs release and CD147 expression on Migs surface, which is related to sorafenib resistance in HCC. Further investigations revealed that hypoxia-induced migrasomes (hypo-Migs) induce VM formation, thereby promoting sorafenib resistance in HCC. Notably, hypo-Migs are internalized into HCC cells through macropinocytosis, which depends on the expression of lysophosphatidic acid receptor 6 (LPAR6). Mechanistically, CD147-positive (CD147 + ) hypo-Migs activate the PI3K/AKT/TWIST1 signaling pathway, subsequently inducing VM formation and promoting sorafenib resistance. Importantly, dual blockade of CD147 + -hypo-Migs macropinocytosis and VM formation enhances the sorafenib-killing efficacy to HCC. Conclusively, our findings uncover a novel sorafenib resistance mechanism induced by CD147 + -hypo-Migs, and highlight dual-targeting of macropinocytosis and VM as a promising strategy to overcome the sorafenib resistance in HCC.
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PubMed
高影响因子
Journal of Extracellular Vesicles
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2023
·Vol. 12
·期 1
·12300
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IF 16
Zhaowei Zhang,Xuehui Liu,Xiaoqing Yang,Ying Jiang,Ang Li,Jiying Cong,Yuwei Li,Qinjian Xie,Chen Xu,Dingbin Liu
Colorectal cancer (CRC) is one of the most common malignancies that is usually detected late in the clinic. The currently available diagnostic tools for CRC are either invasive or insensitive to early lesions due to the dearth of reliable biomarkers. In this study, we discovered that the extracellular vesicles (EVs) in the faeces of CRC patients can act as a potent biomarker for the non-invasive diagnosis and prognosis of CRC. This finding is based on the identification of two transmembrane proteins—CD147 and A33—on faeces-derived EVs (fEVs) that are intrinsically associated with CRC. The detection results show that the levels of CD147 and A33 on fEVs were upregulated in the CRC patients ( n = 48), dramatically distinguishing them from the healthy donors ( n = 16). The CD147/A33-enriched EVs offer a clinical sensitivity of 89%, much higher than that (40%) of carcinoembryonic antigen (CEA), a clinically-established serum biomarker for CRC diagnosis. In addition, the analysis of longitudinal faeces samples ( n = 29) demonstrated that the CD147/A33-enriched fEVs can be utilized to track the prognosis of CRC. Due to the high compliance of faeces-based detection, the CD147/A33-enriched fEVs could serve as new-generation CRC biomarkers for large-scale, non-invasive CRC screening as well as real-time monitoring of patient outcomes during clinical interventions.
研究领域:
肿瘤学
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胃肠病学
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分子生物学
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临床诊断
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）